Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks

Shi Qiang Wang, Long Sheng Song, Le Xu, Gerhard Meissner, Edward Lakatta, Eduardo Ríos, Michael D. Stern, Heping Cheng

Research output: Contribution to journalArticle

Abstract

For a single or a group of Markov channels gating reversibly, distributions of open and closed times should be the sum of positively weighted decaying exponentials. Violation of this microscopic reversibility has been demonstrated previously on a number of occasions at the single channel level, and has been attributed to possible channel coupling to external sources of free energy. Here we show that distribution of durations of Ca2+ release underlying Ca2+ sparks in intact cardiac myocytes exhibits a prominent mode at ∼8 ms. Analysis of the cycle time for repetitive sparks at hyperactive sites revealed no intervals briefer than ∼35 ms and a mode at ∼90 ms. These results indicate that, regardless of whether Ca2+ sparks are single-channel or multi-channel in origin, they are generated by thermodynamically irreversible stochastic processes. In contrast, data from planar lipid bilayer experiments were consistent with reversible gating of RyR under asymmetric cis (4 μM) and trans Ca2+ (10 mM), suggesting that the irreversibility for Ca2+ spark genesis may reside at a supramolecular level. Modeling suggests that Ca2+-induced Ca2+ release among adjacent RyRs may couple the external energy derived from Ca2+ gradients across the SR to RyR gating in situ, and drive the irreversible generation of Ca2+ sparks.

Original languageEnglish (US)
Pages (from-to)242-251
Number of pages10
JournalBiophysical Journal
Volume83
Issue number1
StatePublished - 2002
Externally publishedYes

Fingerprint

Ryanodine Receptor Calcium Release Channel
Stochastic Processes
Lipid Bilayers
Cardiac Myocytes

ASJC Scopus subject areas

  • Biophysics

Cite this

Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks. / Wang, Shi Qiang; Song, Long Sheng; Xu, Le; Meissner, Gerhard; Lakatta, Edward; Ríos, Eduardo; Stern, Michael D.; Cheng, Heping.

In: Biophysical Journal, Vol. 83, No. 1, 2002, p. 242-251.

Research output: Contribution to journalArticle

Wang, SQ, Song, LS, Xu, L, Meissner, G, Lakatta, E, Ríos, E, Stern, MD & Cheng, H 2002, 'Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks', Biophysical Journal, vol. 83, no. 1, pp. 242-251.
Wang, Shi Qiang ; Song, Long Sheng ; Xu, Le ; Meissner, Gerhard ; Lakatta, Edward ; Ríos, Eduardo ; Stern, Michael D. ; Cheng, Heping. / Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks. In: Biophysical Journal. 2002 ; Vol. 83, No. 1. pp. 242-251.
@article{0debd8fadbf5476096a9b12057fb4d46,
title = "Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks",
abstract = "For a single or a group of Markov channels gating reversibly, distributions of open and closed times should be the sum of positively weighted decaying exponentials. Violation of this microscopic reversibility has been demonstrated previously on a number of occasions at the single channel level, and has been attributed to possible channel coupling to external sources of free energy. Here we show that distribution of durations of Ca2+ release underlying Ca2+ sparks in intact cardiac myocytes exhibits a prominent mode at ∼8 ms. Analysis of the cycle time for repetitive sparks at hyperactive sites revealed no intervals briefer than ∼35 ms and a mode at ∼90 ms. These results indicate that, regardless of whether Ca2+ sparks are single-channel or multi-channel in origin, they are generated by thermodynamically irreversible stochastic processes. In contrast, data from planar lipid bilayer experiments were consistent with reversible gating of RyR under asymmetric cis (4 μM) and trans Ca2+ (10 mM), suggesting that the irreversibility for Ca2+ spark genesis may reside at a supramolecular level. Modeling suggests that Ca2+-induced Ca2+ release among adjacent RyRs may couple the external energy derived from Ca2+ gradients across the SR to RyR gating in situ, and drive the irreversible generation of Ca2+ sparks.",
author = "Wang, {Shi Qiang} and Song, {Long Sheng} and Le Xu and Gerhard Meissner and Edward Lakatta and Eduardo R{\'i}os and Stern, {Michael D.} and Heping Cheng",
year = "2002",
language = "English (US)",
volume = "83",
pages = "242--251",
journal = "Biophysical Journal",
issn = "0006-3495",
publisher = "Biophysical Society",
number = "1",

}

TY - JOUR

T1 - Thermodynamically irreversible gating of ryanodine receptors in situ revealed by stereotyped duration of release in Ca2+ sparks

AU - Wang, Shi Qiang

AU - Song, Long Sheng

AU - Xu, Le

AU - Meissner, Gerhard

AU - Lakatta, Edward

AU - Ríos, Eduardo

AU - Stern, Michael D.

AU - Cheng, Heping

PY - 2002

Y1 - 2002

N2 - For a single or a group of Markov channels gating reversibly, distributions of open and closed times should be the sum of positively weighted decaying exponentials. Violation of this microscopic reversibility has been demonstrated previously on a number of occasions at the single channel level, and has been attributed to possible channel coupling to external sources of free energy. Here we show that distribution of durations of Ca2+ release underlying Ca2+ sparks in intact cardiac myocytes exhibits a prominent mode at ∼8 ms. Analysis of the cycle time for repetitive sparks at hyperactive sites revealed no intervals briefer than ∼35 ms and a mode at ∼90 ms. These results indicate that, regardless of whether Ca2+ sparks are single-channel or multi-channel in origin, they are generated by thermodynamically irreversible stochastic processes. In contrast, data from planar lipid bilayer experiments were consistent with reversible gating of RyR under asymmetric cis (4 μM) and trans Ca2+ (10 mM), suggesting that the irreversibility for Ca2+ spark genesis may reside at a supramolecular level. Modeling suggests that Ca2+-induced Ca2+ release among adjacent RyRs may couple the external energy derived from Ca2+ gradients across the SR to RyR gating in situ, and drive the irreversible generation of Ca2+ sparks.

AB - For a single or a group of Markov channels gating reversibly, distributions of open and closed times should be the sum of positively weighted decaying exponentials. Violation of this microscopic reversibility has been demonstrated previously on a number of occasions at the single channel level, and has been attributed to possible channel coupling to external sources of free energy. Here we show that distribution of durations of Ca2+ release underlying Ca2+ sparks in intact cardiac myocytes exhibits a prominent mode at ∼8 ms. Analysis of the cycle time for repetitive sparks at hyperactive sites revealed no intervals briefer than ∼35 ms and a mode at ∼90 ms. These results indicate that, regardless of whether Ca2+ sparks are single-channel or multi-channel in origin, they are generated by thermodynamically irreversible stochastic processes. In contrast, data from planar lipid bilayer experiments were consistent with reversible gating of RyR under asymmetric cis (4 μM) and trans Ca2+ (10 mM), suggesting that the irreversibility for Ca2+ spark genesis may reside at a supramolecular level. Modeling suggests that Ca2+-induced Ca2+ release among adjacent RyRs may couple the external energy derived from Ca2+ gradients across the SR to RyR gating in situ, and drive the irreversible generation of Ca2+ sparks.

UR - http://www.scopus.com/inward/record.url?scp=0036283762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036283762&partnerID=8YFLogxK

M3 - Article

C2 - 12080116

AN - SCOPUS:0036283762

VL - 83

SP - 242

EP - 251

JO - Biophysical Journal

JF - Biophysical Journal

SN - 0006-3495

IS - 1

ER -